Sustained release of cisplatin from multivesicular liposomes: Potentiation of antitumor efficacy against S180 murine carcinoma

Cisplatin was encapsulated into multivesicular liposomes (MVLs) and the entrapment efficiency, size distribution, and in vitro drug release characteristics of the cisplatin-MVLs were studied. Pharmacokinetics, tissue distribution, and therapeutic efficacy of cisplatin-MVLs were compared against injection of cisplatin solution into mice inoculated with the murine carcinoma 180 (S180) tumor. The results showed that the cisplatin-MVLs were capable of high drug loading (0.1.48:1 mg cisplatin/mg lipid) and high encapsulation efficiency (>80%). The mean diameter of cisplatin-MVLs was 17 pm. In vitro studies of cisplatin-MVLs in saline solution showed that they sustained release of encapsulated drug for >7 days. Cisplatin-MVLs showed higher drug accumulation in the liver, spleen, and tumor regions than cisplatin solution, as well as higher plasma concentrations and a longer circulation time. The therapeutic efficacy of the cisplatin-MVL preparation against S180 tumor-bearing mice is significantly higher than that of cisplatin solution. (C) 2004 Wiley-Liss, Inc. and the American Pharmacists Association.Chemistry, MedicinalChemistry, MultidisciplinaryPharmacology & PharmacySCI(E)PubMed26ARTICLE71718-17249